Evaluation of Immunotoxicity of an Urban Profile of Nitrogen Dioxide: Acute, Subchronic, and Chronic Studies

Abstract

Although a number of studies have demonstrated suppression of extrapulmonary immune responses following exposure to NO₂, a ubiquitous ambient and indoor air pollutant, most of these studies have utilized extremely high concentrations of NO₂ relative to the environment. Our intent was to assess effects of NO₂ on extra-pulmonary immune responses using an environmentally relevant exposure regimen. Rats were exposed for 7, 3, 13, 52, or 78 wk to air or a pattern of NO₂ designed to mimic episodic pollution in urban areas at concentrations 2–5 times those commonly seen in such areas. Daily exposures consisted of 0.5 ppm for 16 h, a 6-h exposure spike during which the concentration rose to 1.5 ppm, remained there for 2 h, and then returned to 0.5 ppm, and a 2-h down time. Rats were exposed to this profile 5 days/wk; weekend exposures did not include the spike. Blood was drawn and spleens were removed at the end of each exposure period. Spleen cells were assessed for natural killer (NK) cell activity and responses to T-cell mitogens, phytohemagglutinin and concanavalin A, and a B-cell mitogen, Salmonella typhimurium glycoprotein. Peripheral blood lymphocyte (PBU responses to T-cell mitogens were also assessed. No histopathologic changes as a result of NO₂ exposure were observed in sections from spleen, femur (including marrow), thymus, and mandibular, peribronchial, and mediastinal lymph nodes taken from similarly treated rats. There were no NoO₂-related changes in mitogen responses, although significant suppression of these responses in both air and NO₂ groups was noted in spleen at 52 and 78 wk, and in PBL at 13, 52, and 78 wk, presumably due to aging. Suppression of NK-cell activity was noted after 3 wk of exposure but not after 1, 13, 52, or 78 wk of exposure. Age did not appear to affect NK-cell activity. The transient suppression of NK-cell activity may be important in light of reports of enhanced susceptibility of mice to challenge with syngeneic tumor cells or murine cytomegalovirus, and suggests that effects of NO₂ on NK-cell activity deserve further study.